Ethyl 3-[(Ethylthio)carbonyl]-4,4,5,5,5-pentafluoropentanoate: A building block towards trifluoromethyl pyrazoles and pyrimidin-4-ones

Article abstract of DOI:10.1055/s-0030-1260976

Reaction of the title substrate with methylhydrazine yields, via a domino process, HF elimination-β-addition/elimination-cyclocondensation, to 3-hydroxy-5-trifluoromethylpyrazol-4-ylacetic acid derivatives. In a similar domino process, reaction with benza

Full text of DOI:10.1055/s-0030-1260976

LETTER
1849
Ethyl 3-[(Ethylthio)carbonyl]-4,4,5,5,5-pentafluoropentanoate: A Building
Block towards Trifluoromethyl Pyrazoles and Pyrimidin-4-ones
Trifluoromethyl
H
é
eterocycle
d
s
from Ethy
r
3-[(Eth
i
carbonyl]-4,4,5,5,
B
5-pentafluorope
nr
tanoate ulé, Jean-Philippe Bouillon,*1 Charles Portella*
Institut de Chimie Moléculaire de Reims, UMR 6229 CNRS, Université de Reims Champagne-Ardenne, UFR Sciences,
BP 1039, 51687 Reims Cedex 2, France
Fax +33(326)913166; E-mail: charles.portella@univ-reims.fr
Received 12 May 2011
This paper is dedicated to Professor Alfredo Ricci on the occasion of his retirement
rivative 2 should be the first intermediate in any reaction
involving basic reagent or reactant. The intermediate 2
may be viewed as a tris(electrophilic) species (Scheme 1).
Michael addition–elimination on the b-carbon bearing
Abstract: Reaction of the title substrate with methylhydrazine
yields, via a domino process, HF elimination–b-addition/elimina-
tion–cyclocondensation, to 3-hydroxy-5-trifluoromethylpyrazol-4-
ylacetic acid derivatives. In a similar domino process, reaction with
benzamidine led mainly to ethyl 4-oxo-2-phenyl-6-trifluorometh- fluorine is an expected process,9 and the chemoselectivity/
ylpyrimidin-4-yl acetate. While pyrazole was obtained in high yield
regioselectivity issue for a reaction with a bis(nucleo-
via a totally chemo- and regioselective process, reaction with ami-
dine led to a mixture of regioisomers.
phile) is a further topic of interest. Finally, the trifunction-
al character of 2 should allow access to heterocycles
bearing an additional functional group for possible further
transformation. We report herein the reaction of the build-
Key words: fluorine, heterocycle, domino reaction, pyrazole, pyri-
midin-4-one
ing block 1 with hydrazines and amidines.
As preliminary experiments, 1 was treated with ammonia
In the wide area of fluorinated compounds of interest for
or triethylamine in order to assess the sensitivity of both 1
pharmaceutical and agrochemical applications,2 nitrogen-
and intermediate 2 to basic/nucleophilic reagent. As de-
containing heterocycles, including trifluoromethyl (TFM)
picted in Scheme 2, ammonia reacted both as base to in-
pyrazoles and TFM pyrimidines play a crucial role, as ex-
duce HF elimination and as nucleophile to trap the
emplified by the large related patent literature. As for non-
unsaturated intermediate 2 and to convert it to the enami-
fluorinated analogues, treatment of a TFM dicarbonyl
no derivative 3.10 The stabilization of 3 by intramolecular
compound with the corresponding bis(nucleophile) is a
hydrogen bonding probably prevents cyclocondensation
classical way to have access to these series,3 but various
with the ethoxycarbonyl moiety. Triethylamine induced
other bis(electrophilic) substrates may be interesting al-
HF elimination, but a proton shift led to the more conju-
ternatives, notably for reaction with better regioselectivity
or for synthesizing compounds with a more complex sub-
stitution pattern.4
O
F
O
F5C2
F5C2
F
SEt
SEt
In the course of our research on the chemistry of perfluo-
roketene dithioacetals,5 we have reported on the synthetic
applications towards various multifunctionalized building
blocks used for the synthesis of TFM heterocycles.6 One
of the more versatile TFM building block is obtained by
F3C
SEt
OEt
SEt
OEt
(– HF)
O
O
1
2
treating the perfluoroketene dithioacetal with a ketone Scheme 1 Building block 1 and tris(electrophilic) intermediate 2
enolate7 or a trimethylsilyl ketene acetal8 to give, via an
addition–elimination sequence followed by an acidic hy-
H
HN
O
drolysis, a 2-TFM-1,4-dicarbonyl derivative. Thus 2-
TFM-4-oxo thiolesters7 or 2-TFM thiosuccinic acid
derivatives8 were obtained from perfluoropropanal dithio-
acetal, and used for the preparation of various TFM
heterocycles. Applying a similar sequence to perfluoro-
butanal dithioacetal afforded 2-pentafluoroethyl (PFE)
succinic derivative 1,8 which is much more than a simple
higher homologue (Scheme 1). Indeed, the additional dif-
luoromethylene is of importance since HF elimination is
much easier so that the tetrafluoroethylidene succinic de-
F3C
SEt
(– HF)
74%
R = H
CO2Et
R3N
3
(i) or (ii)
1
2
(– HF)
O
F
F3C
H
R = Et
SEt
CO2Et
81%
(93% conversion)
4
SYNLETT 2011, No. 13, pp 1849–1852
Advanced online publication: 25.07.2011
DOI: 10.1055/s-0030-1260976; Art ID: S03911ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
1
1
Scheme 2 Reaction of 1 with simple amines. Reagents and conditi-
ons: (i) NH3 (excess), Et2O, 10 min, –10 °C; (ii) Et3N (1 equiv),
PhMe, 16 h, r.t.

1850
C. Brulé et al.
LETTER
gated compound 4.11 This more stable tautomeric form
may compete with 2 in reaction with nucleophiles (vide
infra).
NH
⋅HCl
NH2
Ph
CH2Cl2
1) base
After several attempts with different hydrazines,12 treat-
ment of 1 with methylhydrazine in toluene at 80 °C af-
forded the multisubstituted TFM-pyrazole 6 (Scheme 3)
with a yield of 75% taking into account the recovered
starting material (88% conversion).13 The pendant car-
boxylic ester moiety was easily and quantitatively hydro-
lyzed, leading to the pyrazol-4-yl acetic acid 7
(Scheme 3).14 Compound 6 is the result of a four-step
domino process involving: HF elimination–Michael addi-
tion–fluoride elimination–cyclocondensation. The steps
leading to the intermediate 5 are similar to the ones de-
scribed above for the formation of compound 3. No trace
of the tautomeric pyrazolinone form was detected, nor
was the regioisomeric hydroxypyrazole observed, indicat-
ing that the addition to intermediate 2 occurred exclusive-
ly via the substituted nitrogen. On the other hand, the
cyclocondensation step was totally chemoselective to-
wards the thioester moiety. Finally, the structure of 6 was
confirmed by 2D NMR measurements (1H–13C HMBC
2) 1
O
N
O
N
HN
CO2Et
CF3
+
HN
CF3
Ph
Ph
CO2Et
8
9
Scheme 4 Reaction of building block 1 with benzamidine
Table 1 Reaction of 1 with Benzamidinea
Entry Amidinium Base (equiv) Conversionb Yield (%) Yield (%)
salt (equiv)
of 8c
36 (75)
39
of 9c
1
2
3
2.5
4
KOH (2.2)
KOH (3.5) 100
Et3N (2.5) 100
48
5 (10)
7
1.1
28
25
a Solvent: CH2Cl2–H2O (entries 1 and 2); CH2Cl2 (entry 3).
b Based on recovered (isolated) starting material 1.
c In brackets: yield vs. reacted staring material 1.
1
and H–15N HMBC). Pyrazoles with the 3-hydroxy-5-
TFM (or 3-oxo-5-TFM) substitution pattern were previ-
ously prepared from N-trifluoroacetyl building blocks,15
or from TFM-propargylic esters.16 Such a substitution pat-
tern was also present in compounds reported as hypogly-
cemic agents17 or herbicides.18 The most interesting
aspect of the structures 6 and 7 is the presence, besides the
TFM group, of two additional functions potentially useful
for possible development of analogue series, for example
via peptidic coupling.
pyrimidin-4-ones (Scheme 4 and Table 1). Reaction with
two equivalents of benzamidine (from benzamidinium
hydrochloride + potassium hydroxide) acting as both base
and nucleophile led to two isomeric derivatives, the 6-
TFM pyrimidin-4-one 8 and the 5-trifluoroethyl pyrimi-
din-4-one 9 along with the recovered starting material 1
(entry 1). These products, easily separated, are the result
of a domino process evolving through intermediates 2 and
4, respectively (Scheme 5). Compound 8 was obtained
with a good selectivity and a yield of 75% vs. the convert-
ed starting material.19 Using an excess of benzamidine al-
lowed a total conversion but did not improve the yield
(entry 2). On the other hand, with triethylamine as a base
and only 1.1 equivalents of benzamidine; the two pyrimi-
din-4-ones were produced in similar amounts with a
slightly better overall yield (entry 3). Finally, the former
conditions proved to be the more effective ones for both
selectivity in compound 8 and its yield.
NH2
Me
Me
N
N
SEt
N
MeNHNH2
(2 equiv)
OH
F3C
O
1
F3C
PhMe, 80 °C
(– HF)
(– EtSH)
66%
O
Z
(88% conversion)
OEt
5
6
(Z = CO2Et)
1) aq KOH, EtOH, 80 °C
2) aq HCl
99%
7
(Z = CO2H)
The 5-trifluoroethyl-substituted compound 9 is an unprec-
edented functionalized pyrimidin-4-one of interest. We
Scheme 3 From 1 to 3-hydroxy-5-TFM-pyrazoles 6 and 7
Compound 1 was then assessed as a building block for the
synthesis of pyrimidine derivatives. In the presence of tri-
ethylamine (to generate the unsaturated intermediate 2),
the reaction with urea stopped after HF elimination and
proton shift giving compound 4, isolated in 67% yield. A
complex mixture resulted from reaction with the more nu-
cleophilic thiourea.
Ph
NH
PhC(NH)NH2
HN
COSEt
1
2
8
9
(– HF)
(– EtSH)
F3C
CO2Et
COSEt
NH
F3C
PhC(NH)NH2
Free amidines were generated in situ from their salts in
dichloromethane using potassium hydroxide, before re-
acting with 1. Under such conditions reaction with form-
amidine, acetamidine and guanidine gave intractable
mixtures. Only benzamidine enabled us to have access to
4
(– EtSH)
EtO2C
N
H
Ph
Scheme 5 Reaction pathways towards pyrimidin-4-ones 8 and 9
Synlett 2011, No. 13, 1849–1852 © Thieme Stuttgart · New York

LETTER
Trifluoromethyl Heterocycles from Ethyl 3-[(Ethylthio)carbonyl]-4,4,5,5,5-pentafluoropentanoate
1851
Portella, C. Tetrahedron Lett. 1994, 35, 4357. (b) Bouillon,
J.-P.; Didier, B.; Dondy, B.; Doussot, P.; Plantier-Royon, R.;
Portella, C. Eur. J. Org. Chem. 2001, 187. (c) Portella, C.;
Iznaden, M. J. Fluorine Chem. 1991, 51, 1.
were keen to attempt to reverse the selectivity of the reac-
tion, by reacting directly the precursor 4 with benzami-
dine under similar conditions (Scheme 6). According to
the isolated yields, the selectivity was indeed reversed, but
both conversion and yields were poor (yield of 9: 33% vs.
reacted 4).
(10) Data for Compound 3: oil. 1H NMR (250 MHz, CDCl3): d =
1.25 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2O or CH3CH2S), 1.26 (t,
3JH,H = 7.4 Hz, 3 H, CH3CH2S or CH3CH2O), 2.91 (q, 3JH,H
= 7.4 Hz, 2 H, CH3CH2S), 3.46 (q, 5JH,F = 1.4 Hz, 2 H,
CH2CO), 4.16 (q, 3JH,H = 7.1 Hz, 2 H, CH3CH2O), 7.30 (m,
2 H, NH2). 13C NMR (62 MHz, CDCl3): d = 14.1, 14.5
(CH3CH2O, CH3CH2S), 23.5 (CH3CH2S), 32.0 (CH2CO),
60.9 (CH3CH2O), 99.2 (=CCH2CO), 120.5 (q, 1JC,F = 278.7
Hz, CF3), 143.8 (q, 2JC,F = 31.0 Hz, =CCF3), 171.1 (CO2),
193.5 (COS). 19F NMR (235 MHz, CDCl3): d = –66.9 (s). IR
(film): 3416, 3283, 2982, 1736, 1634, 1176 cm–1. GC–MS
(EI): m/z = 285 [M+], 224, 196, 168, 150, 54.
1) KOH (1.2 equiv)
2) 4
NH
+
8
9
⋅HCl
NH2
(1.5 equiv)
CH2Cl2–H2O
55% conversion
Ph
3%
18%
Scheme 6 Reaction of 4 with benzamidine
In summary, the building block 1 exhibits an interesting
reactivity, giving via a multistep domino reaction trifluo-
romethyl-containing heterocycles bearing additional
functional groups useful for further derivatization. The re-
action with methylhydrazine is effective enough to have a
preparative interest in view of obtaining 5-TFM-3-hy-
droxypyrazoles. The reaction with benzamidine exhibits
interesting features and led to valuable compounds, but
would need further investigation and optimization in or-
der to improve both selectivity and yields.
(11) Data for Compound 4: oil. 1H NMR (250 MHz, CDCl3): d =
1.30, 1.31 (t, 3JH,H = 7.3 Hz, 6 H, CH3CH2O, CH3CH2S), 3.03
(q, 3JH,H = 7.3 Hz, 2 H, CH3CH2S), 4.20 (m, 2 H, CH3CH2O),
5.49 (dq, 2JH,F = 44.0 Hz, 3JH,F = 6.0 Hz, 1 H, CHF), 6.39 (m,
1 H, =CH). 13C NMR (62 MHz, CDCl3): d = 13.8, 14.0
(CH3CH2O, CH3CH2S), 24.2 (CH3CH2S), 61.8 (CH3CH2O),
85.8 (dq, 1JC,F = 196.6 Hz, 2JC,F = 36.0 Hz, CHF), 121.1 (qd,
1JC,F = 282.8 Hz, 2JC,F = 27.8 Hz, CF3), 126.4 (d, 3JC,F = 10.7
Hz, =CH), 141.7 (d, 2JC,F = 16.7 Hz, =CCOS), 163.4 (CO2),
189.9 (d, 3JC,F = 3.2 Hz, COS). 19F NMR (235 MHz, CDCl3):
d = –199.5 (dq, 2JF,H = 44.0 Hz, 3JF,F = 12.1 Hz, 1 F, CHF),
–77.5 (dd, 3JF,F = 12.1 Hz, 3JF,H = 6.0 Hz, 3 F, CF3). IR (film):
2984, 2937, 1735, 1670, 1193, 1148 cm–1. GC–MS (EI):
m/z = 288 [M+].
Acknowledgment
(12) Treatment of compound 1 with hydrazine monohydrate or
phenylhydrazine led to low conversions (<10–15%) even
when the reaction mixture was refluxed for several hours.
(13) Preparation of Pyrazole 6: To a solution of compound 1
(0.20 g, 0.6 mmol) in toluene (5 mL), was added
The authors thank ANRT and CEREP for a grant (CB) and financial
support. They also thank Eric Nicolai for fruitful discussions.
References and Notes
methylhydrazine (76 mL, 1.2 mmol). The resulting mixture
was heated at 80 °C for 1 h. After evaporation of volatiles
under reduced pressure, the crude was purified by silica gel
column chromatography (eluent: petroleum ether–EtOAc
(80:20)] affording 0.10 g (yield: 66%, conversion: 88%) of
pyrazole 6 as a solid; mp 92–94 °C. 1H NMR (250 MHz,
CDCl3): d = 1.27 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2O), 3.53 (s,
2 H, CH2CO2), 3.80 (s, 3 H, NCH3), 4.18 (q, 3JH,H = 7.1 Hz,
2 H, CH3CH2O), 11.1 (br s, 1 H, OH). 13C NMR (62 MHz,
CDCl3): d = 14.1 (CH3CH2O), 27.6 (CH2CO2), 37.5 (NCH3),
61.2 (CH3CH2O), 99.9 (CCH2CO2), 120.0 (q, 1JC,F = 269.9
Hz, CF3), 130.2 (q, 2JC,F = 37.8 Hz, CCF3), 159.3 (COH),
170.5 (CO2). 19F NMR (235 MHz, CDCl3): d = –59.9 (s). IR
(KBr): 3058, 2991, 2648, 1736, 1553, 1294, 1129 cm–1. GC–
MS (EI): m/z = 252 [M+], 206, 179, 110. Anal. Calcd for
C9H11F3N2O3: C, 42.86; H, 4.40; N, 11.11. Found: C, 43.14;
H, 4.49; N, 10.56.
(1) Current address: Laboratoire Sciences et Méthodes
Séparatives EA 3233, Université de Rouen, IRCOF, 76821
Mont Saint Aignan cedex, France. Email: jean-
philippe.bouillon@univ-rouen.fr.
(2) For general reviews, see: (a) Bégué, J.-P.; Bonnet-Delpon,
D. Bioorganic and Medicinal Chemistry of Fluorine; Wiley-
VCH: Weinheim, 2008. (b) Burger, K.; Wucherpfennig, U.;
Brunner, E. Adv. Heterocycl. Chem. 1994, 60, 1.
(c) Fluorine in Bioorganic Chemistry; Welch, J. T.;
Eswarakrishnan, S., Eds.; John Wiley & Sons: New York,
1991.
(3) (a) Kumar, V.; Aggarwal, R.; Singh, S. P. Heterocycles
2008, 75, 2893. (b) Sloop, J. C.; Bumgardner, C. L.;
David Loehle, W. J. Fluorine Chem. 2002, 118, 135.
(4) For some reviews, see: (a) Plantier-Royon, R.; Portella, C.
Targets Heterocycl. Syst. 2006, 10, 114. (b) Zhu, S. Z.;
Wang, Y. L.; Peng, W. M.; Song, L. P.; Jin, G. F. Curr. Org.
Chem. 2002, 6, 1057. (c) Uneyama, K. J. Fluorine Chem.
1999, 97, 11.
(5) Muzard, M.; Portella, C. J. Org. Chem. 1993, 58, 29.
(6) Portella, C.; Bouillon, J.-P. in ‘Fluorine-Containing
Synthons’; Soloshonok, V. A., Ed.; ACS Symposia in print
No. 911, American Chemical SocietyOxford University
Press: Washington / D.C., 2005, Chap. 12, 232–247.
(7) (a) Huot, J. F.; Muzard, M.; Portella, C. Synlett 1995, 247.
(b) Hénin, B.; Huot, J. F.; Portella, C. J. Fluorine Chem.
2001, 107, 281. (c) Bouillon, J. P.; Hénin, B.; Huot, J. F.;
Portella, C. Eur. J. Org. Chem. 2002, 1556.
(14) Data for compound 7: solid; mp 210–213 °C. 1H NMR (250
MHz, acetone-d6): d = 3.51 (s, 2 H, CH2CO2H), 3.77 (s, 3 H,
NCH3). 13C NMR (62 MHz, acetone-d6): d = 27.6
(CH2CO2H), 38.0 (NCH3), 101.3 (CCH2CO2H), 121.3 (q,
1JC,F = 268.8 Hz, CF3), 129.7 (q, 2JC,F = 37.2 Hz, CCF3),
159.4 (COH), 172.0 (CO2H). 19F NMR (235 MHz, acetone-
d6): d = –58.7 (s). IR (KBr): 3062, 2966, 2644, 1712, 1185,
1123, 1037 cm–1. HRMS (ESI): m/z [M + H]+ calcd for
C7H8F3N2O3: 225.0487; found: 225.0488.
(15) (a) Lakontseva, E.; Krasavin, M. Tetrahedron Lett. 2010, 51,
4095. (b) Bouillon, J.-P.; Ates, C.; Janousek, Z.; Viehe, H.
G. Tetrahedron Lett. 1993, 34, 5075.
(8) Brulé, C.; Bouillon, J.-P.; Portella, C. Tetrahedron 2004, 60,
9849.
(16) Hamper, B. C. J. Fluorine Chem. 1990, 48, 123.
(9) (a) Dondy, B.; Doussot, P.; Iznaden, M.; Muzard, M.;
Synlett 2011, No. 13, 1849–1852 © Thieme Stuttgart · New York

1852
C. Brulé et al.
LETTER
(17) (a) Kees, K. L.; Fitzgerald, J. J.; Steiner, K. E.; Mattes, J. F.;
Mihan, B.; Tosi, T.; Mondoro, D.; McCaleb, M. L. J. Med.
Chem. 1996, 39, 3920. (b) Kees, K. L. U.S. Patent, US
5264451, 1993; Chem. Abstr. 1993, 120: 95803.
(18) Moedritzer, K.; Rogers, M. D. Eur. Patent, EP0370990,
1990; Chem. Abstr. 1990, 114: 6497.
(19) Preparation of Pyrimidin-4-ones 8 and 9: To a suspension
of benzamidine hydrochloride (1.20 g, 6.5 mmol) in a
mixture of CH2Cl2–H2O (5:1; 6 mL) was added KOH (0.32
g, 5.7 mmol). The resulting mixture was stirred at r.t. for 30
min. Compound 1 (0.50 g, 1.6 mmol) was then added and the
mixture was stirred at r.t. for 10 h. The crude mixture was
washed with H2O (3 mL) and the organic layer was
7.50–7.70 (m, 3 H, Ph), 8.20–8.40 (m, 2 H, Ph), 13.30 (br m,
1 H, NH). 13C NMR (62 MHz, CDCl3): d = 14.1 (CH3CH2O),
30.7 (CH2CO2), 61.4 (CH3CH2O), 119.4 (CCH2CO2), 121.2
(q, 1JC,F = 277.0 Hz, CF3), 127.9 (2 × CH of Ph), 129.1 (2 ×
CH of Ph), 130.6 (Cq of Ph), 132.8 (CH of Ph), 150.8 (q, 2JC,F
= 34.0 Hz, CCF3), 155.9 (C-2), 165.4 (CON), 169.3 (CO2).
19F NMR (235 MHz, CDCl3): d = –65.9 (s). IR (KBr): 3084,
2997, 1741, 1652, 1555 cm–1. Anal. Calcd for
C15H13F3N2O3: C, 55.22; H, 4.02; N, 8.59. Found: C, 54.99;
H, 3.92; N, 8.39.
Compound 9: solid; mp 222–225 °C. 1H NMR (250 MHz,
CDCl3): d = 1.45 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2O), 3.89 (q,
3JH,F = 10.5 Hz, 2 H, CH2CF3), 4.49 (q, 3JH,H = 7.1 Hz, 2 H,
CH3CH2O), 7.50–7.70 (m, 3 H, Ph), 8.20–8.30 (m, 2 H, Ph),
13.3 (br m, 1 H, NH). 13C NMR (62 MHz, CDCl3): d = 14.0
(CH3CH2O), 28.8 (q, 2JC,F = 31.7 Hz, CH2CF3), 62.6
(CH3CH2O), 115.3 (q, 3JC,F = 2.7 Hz, CCH2CF3), 120–130
(m, CF3), 128.0 (2 × CH of Ph), 129.0 (2 × CH of Ph), 130.8
(Cq of Ph), 132.9 (CH of Ph), 155.0, 156.8 (C-2, C-6), 164.9,
165.2 (CON, CO2). 19F NMR (235 MHz, CDCl3): d = –65.0
(t, 3JF,H = 10.5 Hz). IR (KBr): 3432, 2969, 1745, 1547 cm–1.
GC–MS (EI): m/z = 327 [M+], 281, 220, 205, 145.
separated. The aqueous phase was extracted with CH2Cl2 (3
× 5 mL). The combined organic phases were dried over
Na2SO4, filtered off and concentrated in vacuo leading to a
mixture (6:1) of pyrimidin-4-ones 8 and 9. Pure compounds
8 (0.20 g, yield: 39%) and 9 (0.04 g, yield: 7%) were
obtained by preparative TLC [(Merck silica gel 60 PF254
with gypsum), eluent: petroleum ether–EtOAc (70:30)].
Compound 8: solid; mp 218–221 °C. 1H NMR (250 MHz,
CDCl3): d = 1.24 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2O), 3.83 (s,
2 H, CH2CO2), 4.17 (q, 3JH,H = 7.10 Hz, 2 H, CH3CH2O),
Synlett 2011, No. 13, 1849–1852 © Thieme Stuttgart · New York